Compounds which produce a physiological cool sensation when applied to the skin are known, see for example, “New Compounds with the Menthol Cooling Effect,” H. R. Watson, et al., J. Soc. Cosmet. Chem., 1978, 29, 185-200.
Wei, E. T., et al., J. Pharm. Pharmacol., 1983, 35(2), 110-112, describe a compound named “icilin” for its cool-sensation producing properties, (also known as AG-3-5) or 3-(2-Hydroxy-phenyl)-6-(3-nitro-phenyl)-3,4-dihydro-1H-pyrimidin-2-one, of the formula:

Still other compounds having cooling action have been recently reported, see H. Ottinger, et al., J. Agric. Food Chem., 2001, 49, 5383-5390.
U.S. Pat. No. 4,150,052, discloses menthane carboxamide compounds, for example, of the formula IIa3-1:
that are reported to have a physiological cooling action on the skin.
U.S. Pat. No. 4,070,496, discloses certain phosphine oxide (R1R2R3P═O) compounds and compositions that are reported to have a physiological cooling action on the skin.
U.S. Pat. No. 3,821,221, discloses certain tetrahydropyrimidine-2-one compounds that are reported to have central nervous system activity as depressants or stimulants.
Recently, certain TRP receptors have been shown to have a role in thermosensation, see D. D. McKemy, et al., “Identification of a Cold Receptor Reveals a General Role for TRP Channels in Thermosensation,” Nature, Mar. 7, 2002; 416(6876):52-8. For a recent review of “The TRP Ion Channel Family,” see D. E. Clapham, et al., Nature Reviews, Neuroscience, 2001, 2, 387-396 <www.nature.com/reviews/neuro>. Okazawa et al Neuroscience letters (Apr. 8, 2004), 359(1-2):33-6; Nealen et al Journal of neurophysiology (2003 July), 90(l):515-20; Thut et al., Neuroscience (2003), 119(4): 1071-83.
The gene Trp-p8 was discovered by screening a prostate-specific subtracted cDNA library. The predicted protein has significant homology with the transient receptor potential (Trp) family of Ca2+ channel proteins. Northern blot analysis indicates Trp-p8 expression within normal human tissues is mostly restricted to prostate epithelial cells. In situ hybridization analysis shows that Trp-p8 mRNA expression was at moderate levels in normal prostate tissue and appears to be elevated in prostate cancer. Trp-p8 mRNA was also expressed in a number of non-prostatic primary tumors of breast, colon, lung, and skin origin, whereas transcripts encoding Trp-p8 were hardly detected or not detected in the corresponding normal human tissues (Tsavaler, et al Cancer Research (2001), 61(9):3760-3769).
Immunotherapy of prostate carcinoma (PCa) largely depends on the identification of suitable target antigens that are present in a high percentage of prostate tumors. The putative calcium channel protein, Trp-p8, is associated with loss of Trp-p8 mRNA expression and a significantly shorter time to PSA relapse-free survival. The identification of Trp-p8 is associated with prostate cancer outcome, and suggests an integral role for this receptor in prostate carcinogensis. Immunogenic peptides derived from the prostate-specific protein transient receptor potential-p8 (Trp-p8) that is recognized by cytotoxic T lymphocytes from PCa patients have been reported (Kiessling, et al (2003) Prostate 56(4):270-279; Henshall, et al Cancer Research (2003), 63(14):4196-4203; Fuessel, et al International Journal of Oncology (2003), 23(1):221-228; U.S. Pat. No.2003-108,963 A1). Identification of therapeutic agents effective in the treatment of neoplastic, hyperplastic, and like diseases or conditions continues to be the subject of significant research efforts. Recent work indicates that certain therapeutic agents in combination with certain antibody preparations can be effective in treating angiogenic related disorders, and like diseases or conditions, see for example, U.S. Pat. No. 6,582,959.
There is currently a need for therapeutic agents and methods that are useful to treat diseases and conditions that are associated with regulation of the Trp-p8 receptor. There is also a need for therapeutic agents and treatment methods, which are specific and selective toward cancerous cells and have low cytotoxicity toward healthy cells. There is also a need for therapeutic agents in combination with additional chemotherapeutic agents, including, for example, antibody preparations, and combination therapeutic treatment methods thereof, that are useful to treat diseases and conditions that are associated with regulation of the Trp-p8 receptor.